This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The major cause of morbidity and mortality in sickle cell anemia is vaso-occlusion. Cerebral infarcts in children with sickle cell anemia may impair motor and/or cognitive function. Overt strokes occurring in patients with sickle cell anemia have been characterized by a sudden and persistent onset of motor deficits, resulting in clear recognition and prompt treatment. However, silent cerebral infarcts, defined as an abnormal MRI image of the brain with increased signal intensity in multiple T2 weighted images and no history or physical finding of a focal neurologic deficit lasting more than 24 hours, are the most common form of neurologic injury in children with sickle cell anemia. The only proven therapy for prevention of overt strokes in children with sickle cell anemia who have already had strokes is blood transfusion therapy. Without blood transfusion, patients who have experienced strokes have approximately a 70% risk of a second stroke. With transfusion therapy, there is at least and 85% relative reduction in the frequency of subsequent strokes. The purpose of this study is to determine the effectiveness of blood transfusion therapy for the prevention of new ischemic brain injury in the form of overt stroke or silent cerebral infarct measured by MRI of the brain.